Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene profiling in murine Map3k1 mutant embryonic stem cells

ABSTRACT: Transcriptional profiling of gene expression of embryonic stem cells from mutant Map3k1 mice in comparison to control EL14 cells. The differential expression of specific genes between the mutant and control groups generated from the microarray will give an idea of the molecular mechanisms regulating MAPK signaling in embryonic stem cells.

ORGANISM(S): Mus musculus

SUBMITTER: Tesha Suddason

PROVIDER: E-MTAB-1679 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.

Charlaftis Nikolaos N Suddason Tesha T Wu Xuefeng X Anwar Saba S Karin Michael M Gallagher Ewen E

The EMBO journal 20140926 21

Unlike the other MAP3Ks, MEKK1 (encoded by Map3k1) contains a PHD motif. To understand the role of this motif, we have created a knockin mutant of mouse Map3k1 (Map3k1(m) (PHD)) with an inactive PHD motif. Map3k1(m) (PHD) ES cells demonstrate that the MEKK1 PHD controls p38 and JNK activation during TGF-β, EGF and microtubule disruption signalling, but does not affect MAPK responses to hyperosmotic stress. Protein microarray profiling identified the adaptor TAB1 as a PHD substrate, and TGF-β- or ...[more]

PMID: 25260751

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Project description:Human pluripotent stem cells hold great potential for regenerative medicine, but available cell types have important limitations. While embryonic stem cells derived from fertilized embryos (IVF-ESCs) are considered the "gold standard" of pluripotency, they are allogeneic to potential recipients. Autologous induced pluripotent stem cells (iPSCs) are prone to epigenetic and transcriptional aberrations. To determine whether accumulation of such aberrations is intrinsic to somatic cell reprogramming or secondary to the reprogramming method, we generated a genetically matched collection of human IVF-ESCs, iPSCs, and ESCs derived by somatic cell nuclear transfer (SCNT; NT-ESCs), and subjected them to genome-wide genetic, epigenetic and transcriptional analyses. SCNT-based reprogramming is mediated by the full complement of oocyte cytoplasmic factors, thus closely recapitulating early embryogenesis. NT-ESCs and iPSCs derived from the same somatic donor cells contained comparable numbers of de novo copy number variations (CNVs), suggesting that the two reprogramming methods may not differ significantly in mutagenic or selective pressure. On the other hand, the DNA methylation and transcriptome profiles of NT-ESCs corresponded very closely to those of IVF-ESCs, while iPSCs differed markedly from IVF-ESCs and harbored residual DNA methylation patterns typical of parental fibroblasts, suggesting incomplete reprogramming. We conclude that human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal candidates for cell replacement therapies. 16 matched samples, two IVF-ESCs, five sendai produced iPSC lines, two retro-virus produced iPSC lines, four NT-ESCs, the parental fibroblast line, and the sperm and oocyte donor were genotyped using the Illumina Omni5, which interrogates 4.3 million SNPs across the human genome. Additionally, matched samples from a patient with Leigh syndrome, a NT-ESC line, three iPSC lines, and the parental fibroblast line were genotyped using the Illumina Omni5.

Dataset Information

Gene profiling in murine Map3k1 mutant embryonic stem cells

Publications

The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.

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